ABSTRACT Meibomian glands (MGs) play a critical role in the health and well-being of the ocular surface. MG epithelial cells secrete a lipid mixture (meibum) that provides a clear optical surface for the cornea, interferes with bacterial colonization and retards tear overflow. These MG secretions also promote the stability and prevent the evaporation of the tear film. Conversely, MG dysfunction (MGD), and the resulting meibum insufficiency, destabilize the tear film, increase its osmolarity and evaporation, and are the major cause of dry eye disease (DED) in the world. Given the importance of the human MG, it is amazing that, until recently, almost nothing was known about the regulation of this tissue. Further, there is no global cure for MGD. We hypothesize that certain cationic amphiphilic drugs (CADs) may serve as safe and effective topical treatments for human MGD and the associated evaporative DED. Our goal is to test this hypothesis in the present application. Our specific aims are to: [1] assess the ability of different CADs to induce the differentiation of human MG epithelial cells; [2] determine the capacity of specific CADs to ameliorate obstructive MGD in a mouse model of MGD; and [3] examine whether therapeutic CADs are also able to suppress MGD in vitro. If so, then this cellular model in vitro could be used as a screen for the evaluation of other pharmaceutical candidates for treating MGD. Results from these studies should significantly advance our understanding of the processes by which CADs control the MG in health and disease. In addition, findings may have health relatedness for the eye, because they: (1) explore the regulation of the tear film; and (2) may lead to the identification of novel therapeutic strategies to treat MGD and evaporative DED.